Prediction of Screw Loosening After Dynamic Pedicle Screw Fixation With Lumbar Polyetheretherketone Rods Using Magnetic Resonance Imaging-Based Vertebral Bone Quality Score.

OBJECTIVE: To investigate the correlation between magnetic resonance imaging-based vertebral bone quality (VBQ) score and screw loosening after dynamic pedicle screw fixation with polyetheretherketone (PEEK) rods, and evaluate its predictive value. METHODS: A retrospective analysis was conducted on the patients who underwent dynamic pedicle screw fixation with PEEK rods from March 2017 to June 2022. Data on age, sex, body mass index, hypertension, diabetes, hyperlipidemia history, long-term smoking, alcohol consumption, VBQ score, L1-4 average Hounsfield unit (HU) value, surgical fixation length, and the lowest instrumented vertebra were collected. Logistic regression analysis was employed to assess the relationship between VBQ score and pedicle screw loosening (PSL). RESULTS: A total of 24 patients experienced PSL after surgery (20.5%). PSL group and non-PSL group showed statistical differences in age, number of fixed segments, fixation to the sacrum, L1-4 average HU value, and VBQ score (p < 0.05). The VBQ score in the PSL group was higher than that in the non-PSL group (3.56 ± 0.45 vs. 2.77 ± 0.31, p < 0.001). In logistic regression analysis, VBQ score (odds ratio, 3.425; 95% confidence interval, 1.552-8.279) were identified as independent risk factors for screw loosening. The area under the receiver operating characteristic curve for VBQ score predicting PSL was 0.819 (p < 0.05), with the optimal threshold of 3.15 (sensitivity, 83.1%; specificity, 80.5%). CONCLUSION: The VBQ score can independently predict postoperative screw loosening in patients undergoing lumbar dynamic pedicle screw fixation with PEEK rods, and its predictive value is comparable to HU value.

TRPML1 triggers ferroptosis defense and is a potential therapeutic target in AKT-hyperactivated cancer.

Targeting ferroptosis for cancer therapy has slowed because of an incomplete understanding of ferroptosis mechanisms under specific pathological contexts such as tumorigenesis and cancer treatment. Here, we identify TRPML1-mediated lysosomal exocytosis as a potential anti-ferroptotic process through genome-wide CRISPR-Cas9 activation and kinase inhibitor library screening. AKT directly phosphorylated TRPML1 at Ser343 and inhibited K552 ubiquitination and proteasome degradation of TRPML1, thereby promoting TRPML1 binding to ARL8B to trigger lysosomal exocytosis. This boosted ferroptosis defense of AKT-hyperactivated cancer cells by reducing intracellular ferrous iron and enhancing membrane repair. Correlation analysis and functional analysis revealed that TRPML1-mediated ferroptosis resistance is a previously unrecognized feature of AKT-hyperactivated cancers and is necessary for AKT-driven tumorigenesis and cancer therapeutic resistance. TRPML1 inactivation or blockade of the interaction between TRPML1 and ARL8B inhibited AKT-driven tumorigenesis and cancer therapeutic resistance in vitro and in vivo by promoting ferroptosis. A synthetic peptide targeting TRPML1 inhibited AKT-driven tumorigenesis and enhanced the sensitivity of AKT-hyperactivated tumors to ferroptosis inducers, radiotherapy, and immunotherapy by boosting ferroptosis in vivo. Together, our findings identified TRPML1 as a therapeutic target in AKT-hyperactivated cancer.

Timing of decompression in central cord syndrome: a systematic review and meta-analysis.

PURPOSE: This study compared the recovery of motor function and the safety of early and delayed surgical intervention in patients with central cord syndrome (CCS). METHODS: PubMed, Embase, Cochrane Library, and Web of Science were employed to retrieve the targeted studies published from inception to February 19, 2023. Comparative studies of early versus delayed surgical decompression in CCS based on American Spinal Injury Association motor score (AMS) recovery, complication rates, and mortality were selected. The statistical analyses were performed using STATA 16.0 and RevMan 5.4. RESULTS: Our meta-analysis included 13 studies comprising 8424 patients. Results revealed that early surgery improved AMS scores significantly compared with delayed surgery, with an increase in MDs by 7.22 points (95% CI 1.98-12.45; P = 0.007). Additionally, early surgery reduced the complication rates than delayed surgery (OR 0.53, 95% CI 0.42-0.67, P < 0.00001). However, no significant difference was observed in mortality between the two groups (OR 0.97; 95% CI 0.75-1.26; P = 0.84). CONCLUSIONS: Early surgical decompression for CCS can improve motor function and reduce the incidence of complications without affecting the mortality rate in patients. Future research should focus on investigating and analyzing the optimal window period for early CCS surgery. Additionally, the timing of surgery should be determined based on the patient's condition and available medical resources.

Adverse independent prognostic effect of initial lung cancer on female patients with second primary breast cancer: a propensity score-matched study based on the SEER database.

OBJECTIVE: To investigate the prognostic impact of initial lung cancer (LC) on second primary breast cancer after LC (LC-BC) and further develop a nomogram for predicting the survival of patients. METHODS: All patients diagnosed with LC-BC and first primary BC (BC-1) during 2000-2017 were collected from Surveillance, Epidemiology, and End Results database. Pathological features, treatment strategies and survival outcomes were compared between LC-BC and BC-1 before and after propensity score matching (PSM). Cox regression analysis was performed to identify the prognostic factors associated with LC in patients with LC-BC. Additionally, least absolute shrinkage and selection operator regression analysis was used to select clinical characteristics for nomogram construction, which were subsequently evaluated using the concordance index (C-index), calibration curve and decision curve analysis (DCA). RESULTS: 827 429 patients with BC-1 and 1445 patients with LC-BC were included in the analysis. Before and after PSM, patients with BC-1 had a better prognosis than individuals with LC-BC in terms of both overall survival (OS) and breast cancer-specific survival (BCSS). Furthermore, characteristics such as more regional lymph node dissection, earlier stage and the lack of chemotherapy and radiation for LC were found to have a stronger predictive influence on LC-BC. The C-index values (OS, 0.748; BCSS, 0.818), calibration curves and DCA consistently demonstrated excellent predictive accuracy of the nomogram. CONCLUSION: In conclusion, patients with LC-BC have a poorer prognosis than those with BC-1, and LC traits can assist clinicians estimate survival of patients with LC-BC more accurately.

The application of stem cell sheets for neuronal regeneration after spinal cord injury: a systematic review of pre-clinical studies.

BACKGROUND: Stem cell sheet implantation offers a promising avenue for spinal cord injury (SCI) and is currently under investigation in pre-clinical in vivo studies. Nevertheless, a systematic review of the relevant literature is yet to be performed. Thus, this systematic review aims to explore the efficacy of stem cell sheet technology in treating SCI, as indicated by experimental animal model studies. METHODS: We searched PubMed, EMBASE, and Web of Science. Manuscripts that did not pertain to in vivo pre-clinical studies and those published in non-English languages were excluded. A risk assessment for bias was performed using the SYRCLE tool. Extracted data were synthesized only qualitatively because the data were not suitable for conducting the meta-analysis. RESULTS: Among the 847 studies retrieved from electronic database searches, seven met the inclusion criteria. Six of these studies employed a complete transection model, while one utilized a compression model. Stem cell sources included bone marrow mesenchymal stem cells, stem cells from human exfoliated deciduous teeth, and adipose-derived mesenchymal stem cells. In all included studies, stem cell sheet application significantly improved motor and sensory functional scores compared to intreated SCI rats. This functional recovery correlated with histological improvements at the injury site. All studies are at low risk of bias but certain domains were not reported by some or all of the studies. CONCLUSION: The results of our systematic review suggest that stem cell sheets may be a feasible therapeutic approach for the treatment of SCI. Future research should be conducted on stem cell sheets in various animal models and types of SCI, and careful validation is necessary before translating stem cell sheets into clinical studies.

The protective effect of Wnt3a on inflammatory response in oxygen-glucose deprivation/reoxygenation (OGD/R) astrocyte model.

Involving in the immune response after cerebral infarction, astrocytes could secrete large amounts of pro- and anti-inflammatory factors. The aim of this study is to investigate the effect of Wnt3a intervention on the inflammatory response of oxygen-glucose deprivation (OGD) followed by reoxygenation (OGD/R) astrocyte model, and to provide a new target for immunoprotective treatment of cerebral infarction. We constructed the OGD/R rat astrocyte model, the astrocytes were treated by different concentrations of glucose (25, 50, 100 mM) intervened with/without Wnt3a (25 µg/ml). Microscope was used to observe the cell survival in rat astrocytes. The relative expression of inflammatory factors (TNF-a, IL-6, HIF-a) in rat astrocytes was detected by qRT-PCR. The expression of inflammatory factors such as TNF-a, IL-6 and HIF-a in rat astrocytes was increased after OGD/R treatment. The Wnt3a intervention promoted cell survival and decreased the expression of inflammatory factors in rat astrocytes induced by OGD/R. There is a neuroprotective effect that Wnt3a intervention could reduce inflammatory response in the OGD/R rat astrocyte model.

Adjuvant transarterial chemoembolization timing after radical resection is an independent prognostic factor for patients with hepatocellular carcinoma.

Background: It has been reported that postoperative adjuvant TACE (PA-TACE) treatment decreases recurrence and significantly improves the survival of patients who undergo radical resection of hepatocellular carcinoma (HCC) with high-risk recurrence factors. However, when to perform PA-TACE has not been fully studied. Methods: We retrospectively collected the clinicopathologic characteristics of the patients with HCC between October 2013 and June 2020. The optimal cutoff value for PA-TACE time was determined based on the R package "maxstat". Logistic regression and Cox regression analysis were used to determine the effect of the choice of PA-TACE timing on prognosis. Results: The analysis was performed on 789 patients with HCC, and 484 patients were finally involved and were divided into training cohort (378) and validation cohort (106). The PA-TACE timing was found to be associated with survival outcomes. Multivariate logistic analysis found independent predictors of the PA-TACE timing, including gender and history of HBV. Multivariate Cox analysis showed that Ki-67, tumor size, MVI and the PA-TACE timing were independent prognostic factors for RFS in HCC patients. Conclusions: Based on this study, HCC patients with high-risk recurrence factors can receive personalized assistance in undergoing PA-TACE treatment and improve their survival outcomes.

Ambient PM2.5 exposure exacerbates severity of allergic asthma in previously sensitized mice.

OBJECTIVE: Epidemiological studies have shown that elevated concentrations of ambient particulate matter (aerodynamic diameter ≤2.5 µm; PM2.5) correlates with increased incidence of asthma. The aim of this study was to determine whether PM2.5 participates in the exacerbation of asthma. METHODS: Effects of 1, 10 and 100 µg PM2.5 instilled intratracheally in ovalbumin (OVA)-sensitized or asthmatic mice were compared. RESULTS: PM2.5 exposure in the OVA-sensitized and especially asthmatic groups increased Mch responsiveness in a dose-dependent manner. In OVA-sensitized groups, exposure to 1 µg of PM2.5 caused no detectable lung inflammation, while 10 and 100 µg of PM2.5 resulted in a slightly increased trend in numbers of neutrophils and macrophages. Compared with the asthmatic control group, both 10 and 100 µg of PM2.5 provoked a significant increase in eosnophils and neutrophils whereas only 100 µg of PM2.5 noticeably enhanced lymphocytes. In asthmatic groups, administration of 100 µg of PM2.5 greatly increased levels of the pro-inflammatory cytokine TNF-α and Th2-related cytokines IL-4 and IL-10 in bronchoalveolar lavage fluid, but it decreased Th1-related INF-γ. In addition, 10 and 100 µg of PM2.5 exacerbated inflammatory infiltration, goblet cell metaplasia and lung ultrastructure lesions in asthmatic mice. CONCLUSIONS: Our results suggested that acute exposure of PM2.5 could synergize with allergens in the subsequent challenge to aggravate the severity of asthma in sensitized mice, possibly by promoting a Th2-biased immune response.

A mechanistic investigation of the enhanced cleavage at histidine in the gas-phase dissociation of protonated peptides.

Enhanced gas-phase cleavage of peptides adjacent to histidine was investigated. The peptides examined were angiotensins III (RVYIHPF) and IV (VYIHPF) as well as synthetic peptide analogues with altered key residues ((R)VYI-X-Z-F; X = F or H and Z = A, P, or Sar) or a fixed charge M3P(+)CH(2)C(O)-VYIHPF. While all singly protonated peptide ions containing both histidine and arginine fragment nonselectively, the doubly protonated peptide ions with arginine and histidine, and the singly protonated peptides containing histidine but not arginine, cleave in a selective manner. In particular, dominant complementary b+/y+ product ions resulting from cleavage between the HP amide bond are observed. For the fixed-charge derivative, selective cleavage occurs only if a proton is added to produce a doubly charged precursor. The results are consistent with involvement of a protonated histidine in the selective cleavage. The ratio of b+/y+ is determined by the identity of the residue C-terminal to histidine and by the ability of protonated histidine to transfer a proton to the C-terminal leaving fragment. This was probed further by systematically changing the residue C-terminal to histidine and by alkylating histidine. The results indicate that while b+/y+ complementary ion pairs dominate in doubly protonated RVYIHPF, b5(2+) and b6(2+) product ions dominate the spectra of doubly protonated RVYIHAF. Also, dominant b5(2+) product ions are observed when the histidine side chain is alkylated (H) in doubly protonated RVYIHPF. Based on all of the results, a selective fragmentation mechanism for enhanced cleavage at histidine involving an atypical b ion structure is proposed.